Synaptogenesis in the developing embryo is a highly specific and precise process whereby an elaborate neural network is constructed between different sets of neurons and other target cell types. Current advances in cell culture techniques allow us to investigate this process using specific cells in a defined and manipulatable environment. We propose to investigate the biochemical mechanisms underlying the initial steps in synapse formation between sympathetic neuroblastoma cells and/or primary neurons and myocardial cells. These steps will be distinguished as: (a) taxis - the attraction of sympathetic neurites toward their target tissues; (b) adhesion - the means by which neural and muscle cells specifically adhere to each other; and (c) metabolic effects - "trophic" interactions between these cell types which affect the expression of their differentiated characteristics. Taxis will be studied using physically separated cultures grown on semi-solid medium, such that a gradient of metabolites can form between them and the intervening space can be analyzed. Adhesion will be examined using double-labelled monolayer-cell suspension assays. Metabolic effects will be assessed in neural cells by their ability to take up, synthesize, store and release catecholamines; in muscle cells, by their contraction rates. These studies are designed to determine the role in synaptic interactions of nerve growth factor, dopamine Beta-hydroxylase, norepinephrine in combination with alpha and beta adrenergic receptors, and other molecules.